Polymer hydrogels for use as biocompatible or biomimetic substrates, in particular for culturing biological cells and tissues are known. Two-component or multicomponent gels are usually synthesized from a high-molecular polymer as the first component and a low-molecular crosslinking agent as the second component. Known two-component or multicomponent hydrogels with peptide crosslinking have, for example, multi-arm macromolecular structures of polyethylene glycol (PEG), which are crosslinked via short linear peptides. The crosslinking agent molecules are known to have a linear molecular structure. They have at least two, preferably terminal, bond functions of a first type, for example, a thiol function, which conjugate with complementary bond functions of a second type, for example, a maleimide function, of the polymers to be crosslinked, for example, PEG, PVA, albumin or dextran, thus forming a crosslinked gel.
Such hydrogels may also be designed to be biodegradable by the metabolic activity of the cells cultured therein or cleavable by other time-dependent processes. This cleavability allows the hydrogel matrix to be replaced by an extracellular matrix (ECM) formed by the cells themselves in the course of culturing and/or the migration of cells into the hydrogels. To achieve biodegradability or cleavability of the hydrogels, it is known that they can be produced with peptide crosslinking agents composed of linear peptides. The peptides are cleavable by bioactive molecules in particular enzymes such as peptidases or proteinases, for example, matrix metalloproteinases (MMP). The hydrogel structure is dissolved again by intramolecular cleavage of the crosslinking agent.
The main disadvantage of known hydrogels is that the concentration of the crosslinking agent peptides must be high, i.e., more than 10 mmol/liter in any case, usually 20 mmol/liter or more, to form a stable hydrogel which is suitable in particular for cell culturing. Known crosslinking agent peptides are expensive to produce. The high concentration of crosslinking agent also has a negative effect on the possibility of adding other soluble components to the hydrogel during production and reduces the water content of the hydrogel. Such known crosslinked hydrogels therefore need to be improved.